Autophagy can promote cell survival or cell death, but the molecular basis underlying its dual role in cancer remains obscure. Here we demonstrate that Δ9-tetrahydrocannabinol (THC), the main active component of marijuana, induces human glioma cell death through stimulation of autophagy. Our data indicate that THC induced ceramide accumulation and eukaryotic translation initiation factor 2α (eIF2α) phosphorylation and thereby activated an ER stress response that promoted autophagy via tribbles homolog 3–dependent (TRB3-dependent) inhibition of the Akt/mammalian target of rapamycin complex 1 (mTORC1) axis. We also showed that autophagy is upstream of apoptosis in cannabinoid-induced human and mouse cancer cell death and that activation of this pathway was necessary for the antitumor action of cannabinoids in vivo. These findings describe a mechanism by which THC can promote the autophagic death of human and mouse cancer cells and provide evidence that cannabinoid administration may be an effective therapeutic strategy for targeting human cancers.

“A look at the development of SATIVEX, the cannabis derived medicine being grown at the secret location known as Porton Down. Only now was the existence of CBD (Cannabidiol) and its anti-psychotic properties mentioned, and the claim made that some of the newer recreational strains contain no CBD at all (which isn’t actually correct, although CBD levels are low in some strains). A good case for the proper regulation of the commercial trade was almost made, but avoided.” – The UKCIA News Blog